兰索拉唑有关物质的合成

Synthesis of the Impurities of Lansoprazole

目的为加强对兰索拉唑原料药和制剂产品的质量控制,合成存在于该药品中的3个有关物质。方法以2-氯甲基-3-甲基-4-(2,2,2-三氟乙氧基)吡啶盐酸盐和2-巯基苯并咪唑为起始原料,用化学法合成2-{[3-甲基-4-(2,2,2-三氟乙氧基)-2-吡啶基]甲基硫代}-1H-苯并咪唑(1),2-{[3-甲基-1-氧-4-(2,2,2-三氟乙氧基)-2-吡啶基]甲磺酰基}-1H-苯并咪唑(2),2-{[3-甲基-4-(2,2,2-三氟乙氧基)-2-吡啶基]甲磺酰基}-1H-苯并咪唑(3)。结果在甲醇钠的作用下起始原料经缩合得到(1),收率97%。化合物1与两倍摩尔量的间氯过氧苯甲酸(m-CPBA)先在0℃下反应1h,再在25℃下反应3h氧化得到(2),收率91%;化合物1与两倍摩尔量的m-CPBA在-15℃的作用下,氧化得到(3),收率58%,本实验结果经质谱、核磁等确证。结论本实验反应条件温和,原料易得,操作简单,收率高,同时由于溶剂和试剂单一,利于回收套用,降低成本,减少污染。

OBJECTIVE To synthesize three impurities for improving strengthen quality control of raw material and medicinal preparation of lansoprazole. METHODS 2- { [ 3-methyl -4-（2,2,2-trifluoroethoxy） pyridine-2-yl ] methyl sulphanyl } -1H-benzimid- azole（ 1 ） , 2-1 [ 3-methyl-i - oxido 4-（ 2,2,2-trifluoroethoxy ） pyridine-2-yl ] methyl sulphinyl } -1H-benzimidazole （ 2 ）, 2-{ [ 3-methyl-4- （2,2,2-trifluoroethoxy） pyridine-2-yl] methyl sulphonyl } - 1H-benzimidazole （3） were synthesized with 2-chloromethyl-3-methyl-4-（ 2, 2,2-trifluoro-ethoxy） pyridine and l tl-Benzoimidazole-2-thiol. RESULTS Compound 1 was obtained from 2-chloromethyl-3-methyl-4- （2,2,2-trifluoro-ethoxy） pyridine and IH -Benzoimidazole-2-thiol by condensation with 97% yield compound 2 was obtained by the ox- idation of compound 1 with m-CPBA and in 91% yield was reached compound 3 was prepared by oxidation with m-CPBA in 58%. CONCLUSION This synthetic route is simple,reaction conditions are mild and raw malerials are cheap and easy to obtain. This method has the advantages of reducing the cost of production.